The goal of this research is to investigate the possibility that semi-synthetic aminoglycosides bearing aziridine rings will offer a new approach to overcoming the problem of R-factor mediated bacterial resistance. Such resistance occurs because enzymes elaborated by resistant strains cause phosphorylation, adenylylation, or other transformations which inactivate the aminoglycosides. However, aminoglycosides with aziridine rings at the points of enzymic attack might specifically and irreversibly bind to these enzymes and thus permit other aminoglycosides to attack the bacterial ribosomes. The aziridinoaminoglycosides might be antibiotics as well, since they could selectively and irreversibly bind the bacterial ribosomes. For this pilot study, derivatives of kanamycin B with aziridine rings at the 2', 3'-position (3' is a site of phosphorylation) and the 2", 3"-position (2" is adenylylated) will be prepared and tested against suitable strains of gram (minus) bacteria. This study is limited to two years because we are new in this field. If the idea is successful it could easily be extended to other aminoglycosides. This is a new project, not a revision of AI 12094. That application, approved but not funded, contained ideas which were investigated independently at the Schering Corp. and led to active new antibiotics based upon garosamine. Thus there is little left to investigate in that application.